Antimicrobial peptides in human synovial membrane as (low-grade) periprosthetic joint infection biomarkers.
Arthritis, Infectious
/ diagnosis
Arthroplasty, Replacement, Hip
/ adverse effects
Germany
/ epidemiology
Humans
Pore Forming Cytotoxic Proteins
/ analysis
Prospective Studies
Prosthesis-Related Infections
/ diagnosis
Staphylococcal Infections
/ diagnosis
Staphylococcus epidermidis
/ isolation & purification
Synovial Membrane
/ metabolism
Antimicrobial peptide (AMP)
Arthroplasty
Biomarker
Cathelicidin (LL-37)
Histological diagnosis
Human beta-defensin (HBD)
Joint replacement
Periprosthetic infection
Synovial membrane
Journal
European journal of medical research
ISSN: 2047-783X
Titre abrégé: Eur J Med Res
Pays: England
ID NLM: 9517857
Informations de publication
Date de publication:
17 Aug 2020
17 Aug 2020
Historique:
received:
16
06
2020
accepted:
30
07
2020
entrez:
18
8
2020
pubmed:
18
8
2020
medline:
4
6
2021
Statut:
epublish
Résumé
Safe diagnosis of periprosthetic joint infection (PJI) is of utmost importance for successful exchange arthroplasty. However, current diagnostic tools show insufficient accuracy in the clinically common and challenging chronic low-grade infections. To close this diagnostic gap, reliable (bio)markers display the most promising candidates. Antimicrobial peptides (AMPs) are part of the innate immune response towards microbial growth. Recently we could show significant intraarticular levels of human cathelicidin LL-37 and β-defensin-3 (HBD-3) with high diagnostic accuracy in PJI synovial fluid. Consequently, these promising biomarkers were evaluated in PJI synovial membrane and synoviocytes, which may significantly facilitate histological diagnosis of PJI to improve outcome of septic joint replacement. In this prospective single-center controlled clinical study (diagnostic level II), consecutive patients with total hip (THR) and knee (TKR) replacements were included undergoing primary arthroplasty (n = 8), surgical revision due to aseptic loosening (n = 9) and septic arthroplasty with coagulase-negative staphylococci (n = 8) according to the criteria of the Musculoskeletal Infection Society (MSIS). Semiquantitative immunohistochemical (IHC) analysis of LL-37, HBD-3 and HBD-2 in synovial membrane and isolated synoviocytes based on Total Allred Score (TS) and Immunoreactive Remmele and Stegner score (IRS) was performed. For statistical analysis, SPSS 26.0/R3.6.3 (p < 0.05) was used. The AMPs LL-37 and HBD-3 were significantly elevated (up to 20×) in synovial membranes from PJI compared to aseptic loosening or primary arthroplasty. The area under the curve (AUC) in a receiver operating characteristic curve analysis was equal to 1.0 for both scores revealing excellent diagnostic accuracy. Isolated synoviocytes as cellular AMP source showed comparable results with a significant LL-37/HBD-3-increase up to 3 × in PJI. In contrast, local HBD-2 levels were negligible (p > 0.23) upon PJI with a lower diagnostic accuracy (AUC = 0.65) in analogy to our previous findings with synovial fluid. Our results implicate AMPs as promising and specific biomarkers for the histological diagnosis of PJI.
Sections du résumé
BACKGROUND
BACKGROUND
Safe diagnosis of periprosthetic joint infection (PJI) is of utmost importance for successful exchange arthroplasty. However, current diagnostic tools show insufficient accuracy in the clinically common and challenging chronic low-grade infections. To close this diagnostic gap, reliable (bio)markers display the most promising candidates. Antimicrobial peptides (AMPs) are part of the innate immune response towards microbial growth. Recently we could show significant intraarticular levels of human cathelicidin LL-37 and β-defensin-3 (HBD-3) with high diagnostic accuracy in PJI synovial fluid. Consequently, these promising biomarkers were evaluated in PJI synovial membrane and synoviocytes, which may significantly facilitate histological diagnosis of PJI to improve outcome of septic joint replacement.
METHODS
METHODS
In this prospective single-center controlled clinical study (diagnostic level II), consecutive patients with total hip (THR) and knee (TKR) replacements were included undergoing primary arthroplasty (n = 8), surgical revision due to aseptic loosening (n = 9) and septic arthroplasty with coagulase-negative staphylococci (n = 8) according to the criteria of the Musculoskeletal Infection Society (MSIS). Semiquantitative immunohistochemical (IHC) analysis of LL-37, HBD-3 and HBD-2 in synovial membrane and isolated synoviocytes based on Total Allred Score (TS) and Immunoreactive Remmele and Stegner score (IRS) was performed. For statistical analysis, SPSS 26.0/R3.6.3 (p < 0.05) was used.
RESULTS
RESULTS
The AMPs LL-37 and HBD-3 were significantly elevated (up to 20×) in synovial membranes from PJI compared to aseptic loosening or primary arthroplasty. The area under the curve (AUC) in a receiver operating characteristic curve analysis was equal to 1.0 for both scores revealing excellent diagnostic accuracy. Isolated synoviocytes as cellular AMP source showed comparable results with a significant LL-37/HBD-3-increase up to 3 × in PJI. In contrast, local HBD-2 levels were negligible (p > 0.23) upon PJI with a lower diagnostic accuracy (AUC = 0.65) in analogy to our previous findings with synovial fluid.
CONCLUSIONS
CONCLUSIONS
Our results implicate AMPs as promising and specific biomarkers for the histological diagnosis of PJI.
Identifiants
pubmed: 32799924
doi: 10.1186/s40001-020-00434-1
pii: 10.1186/s40001-020-00434-1
pmc: PMC7429885
doi:
Substances chimiques
Pore Forming Cytotoxic Proteins
0
Types de publication
Clinical Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
33Subventions
Organisme : Fakultät für Medizin, Technische Universität München (DE)
ID : KKF C08-08
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